Computers Make Big Strides in Predicting Protein Structure

Researchers from the Howard Hughes Medical Institute (HHMI) have shown that there is a a “glimmer of hope” in developing computerized methods to predict protein folding:

“For more than 40 years, people have known the amino acid sequence of a protein specifies its three-dimensional structure, but no one has been able to translate the sequence into an accurate structure,” said senior author David Baker, an HHMI researcher at the University of Washington. “The reason this research is exciting is that we’re showing progress in predicting the structure from the sequence. It’s not that the problem is solved, but that there is hope…”
In the study, a sophisticated computer program folded 17 short strings of amino acids into 100,000 possible variations. When the researchers compared the best predictions to the actual structures solved earlier by other scientists using experimental techniques, they had the same success rate as the best hitters in major league baseball.
“For about one-third of our benchmark set of small proteins, we generated relatively high-resolution structure predictions, with parts of the structures predicted to near-atomic resolution,” said first author Philip Bradley, a postdoctoral fellow in Baker’s lab. “For us, it is a real step forward to achieve structures that are in some way comparable to what you can get by experiments.”
The encouraging results come from a refinement of a sophisticated computer modeling program called Rosetta, first developed several years ago in Baker’s lab. The program works on the premise that proteins collapse into their lowest energy state, like a ball that rolls down a hill until it comes to rest on level ground. The energies of hundreds of thousands of possible shapes generated by the computer are computed, and the lowest energy shape is selected as the prediction.

More in the press release…
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